The goal of this project is to develop an integrated system for MRI-guided precise targeting and accurate ablation of brain tumors by interstitial high intensity focused ultrasound (iHIFU). Between 25-40% of patients with systemic cancer suffer the effect of brain metastases (BM). Treatment of BMs is often multidisciplinary involving open surgery, stereotactic radiosurgery (SRS), whole brain radiation, and/or chemotherapy. A subset of patients are candidates for open surgery and/or SRS. Open surgery via craniotomy in appropriate patients allows for tissue diagnosis, rapid relief of symptoms, and local disease control. The advantage of SRS is that it is non-invasive and avoids complications associated with craniotomy. SRS, however, precludes tissue diagnosis and time to symptom relief is slower. The purpose of the proposed research is to provide a complete new set of tools offering the benefits of craniotomy less invasively by targeting and ablating tumors through an incision less than one inch. The complete set of tools to deliver this therapy thus requires adequate visualization, precise targeting (<1mm), and conformal ablation. The proposed approach is to combine real-time MR-guided robot-assisted delivery of iHIFU with MR thermal imaging (MRTI) feedback. The system uses an MR-compatible robotic manipulator capable of delivering a cannula with the accuracy, reproducibility and efficiency needed to make this therapy a reasonable adjunct, while interstitial high-intensity ultrasound allows for highly precise electronically configurable therapeutic ablation with capability for exact volume (size and shape) control in 3D, from very small (mm) to moderate (several cm) size, without harming nearby critical structures not involved with disease. The significance of the proposed approach is that it offers a less invasive alternative to craniotomy, which provides the advantage over SRS of allowing for tissue diagnosis as well as immediate tumor ablation in difficult to reach regions of the human brain. The clinical focus of the proposed work is on brain metastases (BM), which are solid, well-demarcated from surrounding tissue, and amenable to MR-guided ablations. It is anticipated that successful development of this novel and highly controllable ablation system will eventually lead to future approaches to treat other types of tumors such as meningiomas. The aims of this project are to: 1) develop a MRI-compatible interstitial ultrasonic neuroablation instrument, 2) construct and evaluate an MRI-compatible manipulator for neuroablation instrument delivery and control, 3) develop and integrate computer-based 3D treatment planning and simulation tools, and 4) perform pre-clinical evaluations to confirm accuracy, optimize clinical workflow, and demonstrate successful ablative lesioning in clinically-relevant environment. Successful completion of this project will result in an experimental protocol in place with a veterinary hospital to use iHIFU as part of a treatment paradigm for canines with brain metastases, with human studies soon to follow.